Medicinal tablet



1962 c. L. BOSWELL 3,048,526

MEDICINAL TABLET Filed Aug. 4, 1958 /l//ll//l//l//l/l/ 22 I z OT 5 NV.

!e e& 14 13 12 3,048 526 Fatented Aug. 7, 1962 &948,526 MEDECINAL TABLETCharles L. Bosweil, Lincoln, Nebr., assignor to The Wander Company,Chicago, ill., a corporation of Deiaware Filed Ang. 4, 1953, Ser. No.'752,768 4 Ciaims. (Cl. 167--82) This invention relates to a novel andimproved me dicinal tablet and more particularly to a tablet of the typecontaining substantially segregated quantities of the same or differentingredients.

lt is frequently desired to provide medicinal or pharmaceuticalcompositions in solid dosage unit form wherein each dosage unit containssegregated quantities of the ingredients of the preparation. Forexample, one type ot' medicinal tablet or pill which is useful fordelayed action or multiple dosage medication is the so-calledtablet-wi-thin-a-tablet or double tablet Construction which consists ofan innermost core tablet, a thin enteric coating around the core tablet,and an outermost shell or layer. Upon oral administration, the medicinalingredients in the outermost shell are readily assimilated in thegastro-intestinal tract to pro-vide immediate therapy. After apredetermined period of time, the gastrointestinal fluids dissolve theenteric coatin on the inner core portion of the tablet and theingredients of the latter are. then available for assimilation. Thus, 'asustained or delayed action eifect is realized which is equivalent tothe result which would be obtained by repeated administration ofconventional tablets over a period of time. Another type of medicinaltab-let which is also employed in certain instances is the so-calledlayered tablet which consists of two or more superimposed layers ofmedicinal ingredients compressed together to form a unitary tablet. Alayered or multiple compressed tablet of this type is used primarily insit-uations where it is necessary to separate or segregate two differentpharmaceutical ingredients which are to be administered at the same timebut which have an adverse effect upon each other so that they cannot beintimately commingled beforehand. For example, an acidic medicinalingredient may have a detrimental ettect on a companion ingredient whichis susceptible to acid action.

However, both the tablet-within-a tablet and the layered tabletconstructions have serious limitations. For example, in thetablet-within-a-tablet the inherent geometry of the Construction is suchthat the quantity of mea that the tablet-within-a-tablet Constructionavoids this dicinal ingredient or ingredients forming the outer shell ofthe tablet is always substantially greater than the quantity of materialforming the inner core of the table-t. In a typical instance, the dosagecontent in the outer shell may be as much as twice as great as thedosage content of the inner core tablet. Moreover, in thetablet-withina-tablet Construction it is necessarily the outer shellportion of the tablet which is first released and assimilated in thegastrointestinal traot. It will readily be understood that theselimitations may frequently restrict the scope and utility of this tabletform.

In the layered tablet, the chief disadvantages are an undesirablemerging of the ingredients at the interface between the layers and alsoa poor degree of control over the relative quantities of the ingredientsin the respective layers. These disadvantages are occasioned by thenecessity of producing a layered tablet in a single compression step soas to o btain a unitary tablet having the required mechanical strengthand coherence. Generally speaking, the layered tablet is formed 'bysuccessively introducng into a die cavity measured amounts of therespective granulated ingredients so as to form two or moresuperirnposed layers of the several ingredients. After the die cavity isfilled, a plunger compresses latter difliculty because the inner core'portion is preformed in a first tabletting or compression operation andthereafter the outer shell is compressed around the preformed core sothat there is 'no merging under pressure of the separate granulations.

In View of the foregoing discussion, it will be seen that there is adecided need for an improved tablet form which afiords the advantages ofboth the tablet-within-atablet and the layered tablet constructionswithout the disadvantages inherent in each of these known therapeuticforms.

Accor-dingly, a primary object of the invention is to provide a noveland improved form of medicinal tablet of the type adapted to containsubstantially segregated quantities of ingredients.

A further object of the invention is to provide a novel and improvedmedicinal tablet of the aforementioned type which combines theadvantages of the prior `art tablet forms without the disadvantagesthereof.

Another object of the invention is to provide a novel and improvedmedicinal tablet which is particularly adapted to contain incompatibleingredents which must be protected from each other.

' for production on modern high speed taljletting equipment.

Other objects and advantages of the invention will become apparent fromthe subsequent detailed description taken in conjunction with theaccompanying drawing, wherein:

FIG. l is a plan view of a tablet comprising one specific embodiment ofthe present invention;

FIG. 2 is an edge view 'of the tablet shown in FIG. 1;

FIG. 3 is a transverse sectional view as seen along the line 3--3 ofFIG. 1;

FIG. 4 is a view similar to FIG. 3 but showing a modilied form of theinvention;

FIG. 5 is a sectional view similar to FIG.. 3 but showing anotherembodiment of the invention; and

EIG. 6 is a sectional View of still another emb odiment of the inventionReferring first to FIGS. 1 to 3 and 5, a tablet 10 is shown of aconventional overall configuration and having a main body portion 11with an outwardly opening cavity or recess i?. in one side thereof andan inlay portion 13 contained in the `cavity 12 so as to form a unitarytablet construction with the main body portion 11. A modification isshown in FIG. 5 wherein the main body portion 11' extends radiallyinwardly to a slight extent around the marginal edge of the opening ofthe cavity 12 in the side of the tablet so as to provide `an overlyingperipheral lip portion 14- for retaining and mechanically interlockingwith the inlay tablet portion 13. In manufacturing the tablet, the inlayportion 13 is first compressed in a tabletting machine in the usualmanner to provide a compressed preform. This preform is then subjectedto a further tabletting operation of a conventional character whereinanother granulation is compressed around the preform 13 to provide thesurrounding body portion lili.

Inasmuch as both the inlay portion 13 and the main body portion 11 ofthe tablet are formed by independent compression or tabletting steps, itwill be understood that highly accurate control can be exercised overthe quantities of ingredients which form the two parts of the tablet.Furtherrnore, since both the inlay portion 13 and the main body portion11 have exposed outer surfaces, it can readily be arranged to permiteither the portion il or the portion 13 to be released first in thegastrointestinal tract with any desired degree of time delay in therelease or assirnilaton of the other portion of the tablet. in thepresent emhodiment as seen in FIG. 3, dilferential releasability betweenthe portions 11 and 13 of the tablet is realized by using a coatedgranulation for one portion and an uncoated granulation for the otherportion of the tablet. For example, assuming that the inlay portion 13comprisng the smaller dosage of ingredients is to be assrnilated first,the portion 13 may be preformed from an uncoated granulation so thatthis portion is immediately dissolved in the gastrointestinal tract.However, the main body portion 11 of the tablet comprising a largerdosage of the same ingredients may be formulated as coated granulationin which each granular particle has a time delay or enteric coatingdesigned to resist assimilation in the gastrointestinal fluids. Suchcoated granulations are well known in the art and require no detaileddescription. It will also be understood that the same technique ofcoated and uncoated granulations for the inlay and main body portions ofthe tablet may be utilized where the tablet portions contain differentmedicinal ingredients which have an adverse effect on each other andmust, therefore, be protected from each other. Also, it will beappreciated that the larger portion 11 may be formed from an uncoatedgranulation so as to be assimilated first and the smaller inlay portion13 may be formed from a coated granulation for delayed assimilationthereof.

In FIG. 4, a modification of the invention is shown wherein segregatonof the inlay and main body portions of the tablet, for purposes of timedelay or positive separation of incompatible ingredients, is realizedwithout the necessity of employing `a coated granulation for one of thetablet portions. Thus, the preformed inlay portion of the tablet,designated at 16, may be formulated from an uncoated granulatior and isthen surrounded by a thin enteric coating or envelope 17 of aconventional character. The main body portion is desgnated at 18 and mayalso consist of an uncoated granulation which is conipressed around theenteric coated inlay portion lid-17. In this modification of theinvention the main body portion 18 of the tablet is first released andassimilated in the gastrointestinal tract while the enteric coating 17protects the inlay portion 16 for a predetermined period of time so asto provide time delayed or sustained medication.

Of course, in addition to the provision of a separate enteric coating orenvelope for the inlay portion of the tablet as illustrated in FIG. 4,the particles of the granulation in either or both portions of thetablet may be coated to any desired degree so 'as to provide a furtherdegree of control over the time release feature and positive segregationfeature of the tablet construction.

Various enteric coating materials are well known to those skilled in theart and extended discussion thereof is, therefore, unnecessary. :Forexample, the more common enterc coating materials include celluloseacetate phthalate, tolu balsam, carnauba wax, alcoholic shellacsolutions, hydrogenated fats, etc. It will he understood that the samegeneral types of enteric coating materials may be used for coatingeither an entire compressed tablet portion or the individual particlesof a granulation prior to compression.

In FG. 6, a further modification of the invention is shown comprisng atablet having a main body portion and two separate inlay portions atopposite sides of the tablet. Thus, the two oppositely disposed inlayportions are designated at 19 and Zi wit i the main body portion beingdesignated at 22. It will be noted that the inlay portons 19' and 21have exposed surfaces at opposite sides of the tablet and that thematerial comprising the main body portion 22. extends around theperipheral edges of the inlay portions and is also disposed as a thinlayer between the inlay portons so that the latter are completelysegregated from' each other. As will readily be understood, thepreviously discussed advantages of the invention are extended evenfurther by means of the double inlay arrangement. For example, the inlayportions 19 and 21 may conprise the same or dierent pharmaceuticalcompositions and they may be `coated or uncoated so as to provide anydesired sequence of delayed or concurrent release between the respectiveportions 19, Zi, and'ZZ of the tablet in accordance with the meansheretofore described.

Merely by way of illustration, the following specific examples representtypical inlay tablets which may be made in accordance with the presentinvention.

Example I An appetite depressant tablet is formulated in the mannershown in FIGS. 1-3. In the outer layer the particles of the granulationare enteric coated to provide slow release over a period of ten totwelve hours. The inlay portion is formed from an uncoated readilydisintegratable granulation for immediate therapeutic eifectiveness.

The formula for the outer layer is as fcllows:

d-Amphetamine sulfate mg 10 Amobarbital rng 30 Excipients q.s. Entericcoating solution for coatng granulation q.s.

The formula for the inlay portion is as follows:

d-Amphetamine sulfate "mg" 5 Amobarbital mg 15 Excipients q.s. Standardgranulating solution q.s.

Example H An oral decongestant tablet is formulated as in Example I withthe outer layer comprising a coated granulatior and the inlay portion anuncoated granulation.

The formula for the outer layer is as follows:

with an enteric coating or envelope around the inlay portion. Thus, theouter layer is promptly disintegratable for immediate hypnotic efect andthe inlay portion begins to disintegrate after three to four hours tomaintain or continue the desired effect.

Pharmaceutical glaze shellac granulating solution q.s. Enteric eoatingmaterials for coating inlay portion of tablet q.s.

Although in the illustrated embodiments the invention has been describedin connection with tablets having the conventional round shape, it is tobe understood that the features of the invention may also be utilized intablets of different and less conventional shape such as triangular,rectangular, or capsule shaped tablets.

As described above, it will be seen that the invention provides a noveltablet Construction which provides wide flexibility in the compositingof segregated quantities of medicinal ingredients either for purposes oftime delayed medication or protection of inconpatible ingredients fromeach other. At the same time, the tablet form permits of positiveseparation of the segregated areas with accurate control over therelative amounts of the several portions of the tablet. The -finaltablet is readily adapted for varying relative dosages of difierentingredients and varying orders of releasability depending upon thetherapeutic effects desired. Moreover, in most cases conventionaltabletting and compression coating machines will require only relativelyminor modifications to adapt them to the production of inlay tablets asherein described, particularly with respect to FIGS. 1-4. Finally, theinlay construction of the tablet aiords a unique and distinctiveappearance, particularly if the inlay portion of the tablet is of aeontrasting color with respect to the surrounding body portion therebycontributing significant advantages to the tablet constructon bothduring production and merchandising. For example, during production thepresence of an exposed inlay portion of contrasting color with theremainder of the tablet provides instant visual proof that a completetablet has been made and thereby greatly facilitates inspection of thefinal product before ackaging and shippng.

Although the invention has been illustrated and described with respectto certain specific embodiments thereof, it is to be understood thatvarious modifications and alternatives may be resorted to withoutdepart'ng from the scope of the invention as defined in the appendedclaims. r

I claim:

1. A method of making an oral dosage tablet form which comprises;compressing a finely divided medicinal ingredient portion to form acompressed tablet inlay portion having smaller dimensions than thedesired finished tablet form, positioning the preformed compressedtablet inlay portion in contact with a second finely divided medicinalingredient portion, compressing said second medicinal ingredient portionabout only a part of said compressed tablet inlay portion to form acompressed main body portion and exposing only a single surface of saidcompressed tablet inlay portion on the outer surface of the finishedtablet form, and said single surface lying in substantially a commonplane with contiguous portions of said compressed main body portion.

2. An oral dosage tablet form comprising; a compressed tablet inlayportion of a finely divided medicinal ingredient portion with saidcompressed tablet inlay portion having smaller dimensions :than thedesired finished tablet, and a compressed main body portion comprising asecond medicinal ingredient portion compressed about only a part of saidtablet inlay portion with only a single surface of said compressedtablet inlay portion exposed on the outer surface of the finished tabletform and said single surface lying substantially in a common plane withcontiguous portions of said compressed main body portion, and said oraldosage tablet form being made by compressing the first mentioned saidfinely divided medicinal ingredient portion to form said compressedtablet inlay portion, positioning said compressed tablet inlay portionin contact with said second finely divided medicinal ingredient portion,compressing said second medicinal ingredient portion about only a partof said compressed tablet inlay portion to form said compressed mainbody portion and expose only said single surface of said compressedtablet inlay portion on the outer surface of the finished tablet formwith said single surface lying in substantially a common plane withcontiguous portions of said main body portion.

3. An oral dosage tablet form as defined in claim 2, wherein saidfinished tablet form has a second compressed tablet inlay portiondisposed therein with said second compressed tablet inlay portion havingonly a single surface thereof'exposed on the outer surface of saidfinished tablet form.

4. A method of treating a human body with a drug which comprises;administerng to a human host an oral dosage tablet form comprising acompressed tablet inlay portion of a finely divided medicinal ingredientportion with said compressed tablet inlay portion having smallerdimensions than the desired finished tablet form, and a compressed mainbody portion comprising a second medicinal ingredient portion compressedabout only a part of said compressed tablet inlay portion With a singlesurface of said tablet inlay portion exposed on the outer surface ofsaid finished tablet form, and said single surface lying substantiallyin a common plane with contiguous portions of said main body portion.

References Cited in the file of this patent UNITED STATES PATENTS109,677 Seitz Nov. 29, 1870 701,438 Whyte June 3, 1902 1,267,320 FriesMay 21, 1918 `1,5 16,398 McDowell Nov. 3, 1924 1,855,- Jones Apr. 19,1932 2,312,381 Bi'ckenheuser Mar. 2, 1943 '2,809,917 Hermelin Oct. 15,1957 2,951,792 Swintosky Sept. 6, 1960 2,957,804 Shuyler Oct. 25, 19602,987,445 Levesque June 6, 1961 2,991,226 Millar et a-l. July 4, 19612,966,431 Barry Aug; 15, 1961 FOREIGN PATENTS 1,651 Great Britain 1891OTHER REFERENCES Drug and Cosmetic Industry, vol. 7 8, No. 1, articlePress-Coated and Multi-Layer Tablets, by Tsevdos, January 1956, pages38, 39, 40, 113 114.

2. AN ORAL DOSAGE TABLET FORM COMPRISING; A COMPRESSED TABLET INLAYPORTION OF A FINELY DIVIDED MEDICINAL INGREDIENT PORTION WITH SAIDCOMPRESSED TABLET INLAY PORTION HAVING SMALLER DIMENSIONS THAN THEDESIRED FINISHED TABLET, AND A COMPRESSED MAINBODY PORTION COMPRISING ASECOND MEDICINAL INGREDIENT PORTION COMPRESSED ABOUT ONLY A PART OF SAIDTABLET INLAY PORTION WITH ONLY A SINGLE OF SAID COMPRESSED TABLET INLAYPORTION EXPOSED ON THE OUTER SURFACE OF THE FINISHED TABLET FORM ANDSAID SINGLE SURFACE LYING SUBSTANTIALLY IN A COMMON PLANE WITHCONTIGUOUS PORTIONS OF SAID COMPRESSED MAIN BODY BODY PORTION, AND SAIDORAL DOSAGE TABLET FORM BEING MADE BY COMPRESSING THE FIRST MEMTIONEDSAID FINELY DIVIDED MEDICINAL INGREDIENT PORTION TO FORM SAID COMPRESSEDTABLET INLAY PORTION, POSITIONING SAID COMPRESSED TABLET INLAY PORTIONIN CONTACT WITH SAID SECOND MEDICINAL INGREDIENT PORTION, COMPRESSINGSAID SECOND MEDICINAL INGREDIENT PORTION ABOUT ONLY A PART OF SAIDCOMPRESSED TABLET INLAY PORTION TO FORM SAID COMPRESSED MAIN BODYPORTION AND EXPOSE ONLY SAID SINGLE SURFACE OF SAID COMPRESSED TABLETINLAY PORTION ON THE OUTER SURFACE OF THE FINISHED TABLET FORM WITH SAIDSINGLE SURFACE LYING IN SUBSTANTIALLY A COMMON PLANE WITH CONTIGUOUSPORTIONS OF SAID MAIN BODY PORTION.